The extent to which primary DNA sequence effects the degree and specificity of mutagenesis is being determined in a forward/reverse mutational assay employing genetically engineered derivatives of M13mp2. Recent models for the formation of frameshift and deletion formation propose that besides repeated sequences, palindromic DNA sequences may also provide structural intermediates for their formation. The development of recombinant DNA technology allows this possibility to be tested. Various DNA targets are being constructed which differ in one or more of the following ways: a) base composition , e.g., A:T or G:C richness, b) length of a run of same base, c) number of repeats of a common sequence, d) palindromic or quasipalindromic sequences, putatively able to form secondary structures. Mutagenesis of these targets can then be used to monitor DNA sequence alteration and their characterization should yield information on the mechanism of their formation. These DNA constructs will also be analyzed in in vitro studies using purified replication and repair proteins. In addition, the development of plasmid constructs which mutate by a known mechanism will allow an investigation of the role of host DNA metabolism in driving these events.